Nerve cell assemblies in circumscribed regions of the brain, e.g. of the thalamus and the basal ganglia, are pathologically, e.g. excessively synchronously, active in patients with neurological or psychiatric diseases such as Parkinson's disease, essential tremor, epilepsy, functional disturbances after a stroke, dystonia or obsessive compulsive disorders. In this case, a large number of neurons synchronously form action potentials, i.e. the participating neurons fire excessively synchronously. In a healthy person, in contrast, the neurons fire with a different quality, e.g. in an uncorrelated manner, in these brain sectors.
In Parkinson's disease, the pathologically synchronous activity changes the neuronal activity in other brain regions, e.g. in areas of the cerebral cortex such as the primary motor cortex. In this respect, the pathologically synchronous activity in the region of the thalamus and of the basal ganglia, for example, imposes its rhythm on the cerebral cortex areas such that ultimately the muscles controlled by these areas develop pathological activity, e.g. a rhythmic trembling (tremor).
Deep brain stimulation is used to treat Parkinson's patients who cannot be sufficiently treated by medication. In this process, deep electrodes are implanted in specific areas of the brain, e.g. in the subthalamic nucleus. An electrical stimulation is carried out via the deep electrodes to relieve the symptoms. With the standard high-frequency stimulation for treating Parkinson's disease, a so-called high-frequency permanent stimulation is carried out at frequencies of more than 100 Hz. This kind of treatment has no long-lasting therapeutic effects (cf. P. Temperli, J. Ghika, J.-G. Villemure, P. Burkhard, J. Bogousslaysky, and F. Vingerhoets: How do Parkinsonian signs return after discontinuation of subthalamic DBS? Neurology 60, 78 (2003)). “Coordinated reset stimulation” (CR stimulation), that can additionally have long-lasting therapeutic effects, manages with less stimulation current (P. A. Tass, L. Qin, C. Hauptmann, S. Doveros, E. Bezard, T. Boraud, W. G. Meissner: Coordinated reset neuromodulation has sustained after-effects in Parkinsonian monkeys. Annals of Neurology 72, 816-820 (2012); I. Adamchic, C. Hauptmann, U. B. Barnikol, N. Pawelcyk, O. V. Popovych, T. Barnikol, A. Silchenko, J. Volkmann, G. Deuschl, W. Meissner, M. Maarouf, V. Sturm, H.-J. Freund, P. A. Tass: Coordinated Reset Has Lasting Aftereffects in Patients with Parkinson's Disease. Movement Disorders 29, 1679 (2014)).
With other diseases, e.g. epilepsy that cannot be sufficiently treated with medication, different electrodes, e.g. epicortical or epidural electrodes, are also implanted in addition to deep electrodes. With further diseases, e.g. chronic pain syndromes, it is customary to stimulate the spinal cord not only by means of deep electrodes in the brain, but also by means of e.g. epidural electrodes. In contrast to CR stimulation, most other types of stimulation have no long-lasting therapeutic effects.
Therapeutic effects can also be achieved by direct stimulation of the brain tissue or spinal cord by light, e.g. via implanted light-guides. Different spatiotemporal stimulation patters such as CR stimulation can also be used in this respect.
Although the deep brain stimulation by means of invasive CR stimulation enables long-lasting therapeutic effects, this approach has relevant limitations:
(a) Typically, stimulation takes place intermittently, i.e. by means of a plurality of stimulation epochs, to reduce the current input. The intermittent stimulation can reduce the side-effect rate and restrict the total power consumption. Since a considerably reduced power consumption enables the use of a substantially smaller battery or of a corresponding rechargeable battery, it can be made possible in this manner to use particularly small implants that are gentle (with respect to surgical trauma and the risk of infection). The effect of the prior CR stimulation fluctuates by too much from stimulation epoch to stimulation epoch, i.e. there are too many stimulation epochs with an insufficiently pronounced effect. In other words, the stimulation effect is dependent to a relevant degree on the initial conditions of the organism or nervous system in which the stimulation is started. If e.g. a very good effect is achieved in the one stimulation epoch, this effect will rather be unsatisfactory in a next stimulation epoch. To compensate the less effective stimulation epochs, a larger number of stimulation epochs is necessary to build up a good therapeutic effect.
(b) The stimulation success depends too greatly on the stimulus intensity in the previous form of the CR stimulation. Different factors can relevantly modify the stimulus strength. The effective stimulus intensity that actually arrives at the neuronal target population can e.g. fall due to scarring around implanted deep electrodes.
(c) The stimulus strength must very generally be considered in relation to characteristic parameters of the system to be stimulated, that is of the body or of the nervous system. Since these parameters (e.g. specific ion concentrations, fluid volumes, hormone concentrations, etc.) fluctuate and are e.g. subject to pronounced fluctuations at different times of day, an optimum stimulus strength should either be correspondingly corrected or a stimulation method should be used whose stimulation effects are as independent as possible of these fluctuations.
In summary, the effect of the previously used CR stimulation is not sufficiently robust with respect to fluctuations of the stimulus intensity as well as with respect to characteristic parameters of the organism or nervous system to be stimulated (at the start of the stimulation as well as in the course of stimulation) and the effect of the CR stimulation in particular fluctuates by too much from stimulation epoch to stimulation epoch, i.e. there are too many stimulation epochs with a small effect.